To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

Inclusion Criteria:

• Diagnosis of PMF, PPV-MF, or PET-MF.

• DIPSS risk category of intermediate-1, intermediate-2, or high.

• Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8weeks prior to Day 1

• Palpable spleen of ≥ 5 cm below the left costal margin on physical examination atthe screening visit.

• Active symptoms of MF at the screening visit, as demonstrated by the presence of aTSS of ≥ 10 using the Screening Symptom Form.

• Participants with an ECOG performance status score of 0, 1, or 2.

• Screening bone marrow biopsy specimen and pathology report(s) available that wasobtained within the prior 2 months or willingness to undergo a bone marrow biopsy atscreening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.

• Life expectancy of at least 24 weeks.

• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Prior therapy with any drug that inhibits PI3K (examples of drugs targeting thispathway include but are not limited to INCB040093, idelalisib, duvelisib,buparlisib, copanlisib, and umbralisib).

• Use of experimental drug therapy for MF or any other standard drug used for MF (whether for treatment of MF or another indication) with the exception ofruxolitinib, within 3 months of starting study drug, and/or lack of recovery fromall toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.

• Inability to swallow food or any condition of the upper gastrointestinal tract thatprecludes administration of oral medications.

• Recent history of inadequate bone marrow reserve.

• Inadequate liver and renal function at screening.

• Active bacterial, fungal, parasitic, or viral infection that requires therapy.

• Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.

• Known HIV infection.

• Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinionmay jeopardize the safety of the participant or compliance with the Protocol.

• Active invasive malignancy over the previous 2 years.

• Splenic irradiation within 6 months before receiving the first dose of study drug.

• Concurrent use of any prohibited medications.

• Active alcohol or drug addiction that would interfere with the ability to complywith the study requirements.

• Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 halflives(whichever is longer) before the first dose of study drug or anticipated duringthe study.

• Inadequate recovery from toxicity and/or complications from a major surgery beforestarting therapy.

• Currently breastfeeding or pregnant.

• Any condition that would, in the investigator's judgment, interfere with fullparticipation in the study, including administration of study drug and attendingrequired study visits; pose a significant risk to the participant; or interfere withinterpretation of study data.

• History of Grade 3 or 4 irAEs from prior immunotherapy.

• Receipt of any live vaccine within 30 days of the first dose of study drug

• Unwillingness to receive RBC transfusions to treat low hemoglobin levels.

• Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib orexcipients of parsaclisib/matching placebo or ruxolitinib formulations.